Accumulation of DNA damage, as observed in aged human tissues, is one of the molecular causes of aging. Cells respond to DNA damage by activating checkpoints that prevent the contribution of damaged cells to tissue homeostasis by induction of cell death (apoptosis), cell cycle arrest (senescence) or self-digestion of the damaged cells (autophagy). Induction of a DNA damage response (DDR) prevents cancer formation by eliminating genetically instable cells. However, when a growing number of cells in aging tissues accumulates DNA damage, the induction of the same responses can also lead to loss of tissue maintenance and tissue atrophy. The main aims of our current proposal are to delineate the functional influence of the DDR on cellular and tissue aging at different levels and will be studied within a network of collaborating Leibniz Institutes (FMP, IUF, LIN). We hypothesize that specific inhibitors of central players of DDR can be developed for future therapies to promote healthy aging.
Period: 1 January 2014 - 31 December 2016
Contact: Dr. Christoph Kaether
Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Phone.: ++49 (0)3641-65 62 30
Marthandan S, Baumgart M, Priebe S, Groth M, Schaer J, Kaether C, Guthke R, Cellerino A, Platzer M, Diekmann S, Hemmerich P. (2016): Conserved Senescence Associated Genes and Pathways in Primary Human Fibroblasts Detected by RNA-Seq. PLoS One 2016, 11(5), doi: 10.1371/journal.pone.0154531.
Marthandan S, Menzel U, Priebe S, Groth M, Guthke R, Platzer M, Hemmerich P, Kaether C, Diekmann S. (2016): Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence. Biol Res 2016, 49(1), 34. 10.1186/s40659-016-0095-2.